By Ana Espino | Published on February 24, 2026 | 3 min read
Obesity is a major public health
challenge, largely promoted by a food environment rich in energy-dense
products. The regulation of food intake no longer relies solely on classical
homeostatic hunger and satiety circuits. It also involves complex cognitive
mechanisms integrating memory, context, and environmental cues. Past
experiences associated with foods shape dietary choices and can promote
excessive consumption, independently of actual metabolic needs.
Traditionally, the hippocampus (HPC)
is recognized for its central role in spatial and contextual memory. However,
emerging evidence suggests that it also contributes to the control of feeding
behavior. Previous studies have primarily highlighted an inhibitory role of the
hippocampus in food intake, particularly in regulating meal size. Nevertheless,
the precise neuronal mechanisms linking contextual memory to specific
macronutrient preference remained insufficiently defined.
Published in January 2025 in Nature
Metabolism, this study aimed to identify and characterize distinct neuronal
ensembles within the dorsal hippocampus (dHPC) that are specifically activated
by fat or sugar ingestion, and to determine their causal role in shaping
dietary choice and modulating food intake.
Different neurons for sugar and fat ?
The authors used murine models
(C57BL/6J mice, 6–20 weeks old) combined with activity-dependent genetic
tagging to identify dHPC neurons activated following ingestion of specific
nutrients. Targeted stimulation and ablation approaches were employed to assess
the causal role of these neuronal ensembles.
The results reveal the existence of
spatially distinct neuronal populations within the dHPC activated either by
fats or by sugars. Sugar-responsive neurons primarily encode the spatial memory
of sugar location, forming a genuine sugar-specific appetitive engram. Their
activation increases food intake, whereas their suppression impairs
context-driven consumption.
In contrast, fat-responsive neurons
enhance motivation and preference for fatty foods, modulating meal size and
attraction to high-fat diets. Stimulation of these neurons specifically
increases fat consumption, while their ablation reduces hypercaloric food
intake and limits weight gain induced by an obesogenic diet.
The authors also demonstrate a
causal role for the vagus nerve in transmitting post-ingestive signals to the
hippocampus, suggesting the existence of a macronutrient-specific gut–brain
circuit. These findings highlight an unexpected degree of hippocampal
specialization in the control of food consumption.
Memory at the core of dietary choice
Obesity partly results from the
interaction between metabolic signals and contextual food memory. This study
sought to identify hippocampal circuits responsible for macronutrient-specific
consumption.
The findings show that the dorsal
hippocampus integrates sensory, mnemonic, and motivational information through
distinct neuronal ensembles for sugars and fats. Sugar-sensitive neurons encode
the contextual location of sweet foods, whereas fat-sensitive neurons amplify
the motivation to consume them. This functional dissociation reveals the
existence of specialized orexigenic circuits that may promote overconsumption
in environments rich in food-related cues.
By identifying
macronutrient-specific hippocampal circuits, this study opens new avenues for
developing strategies targeting food memory and motivation in order to limit
the consumption of obesogenic foods in modern environments. However, the
results rely exclusively on animal models. Translation to humans requires
further investigation, particularly through functional imaging and
translational neuroscience approaches.
Read next: Liver, sugar, and pills: who's in
control?
About the author – Ana Espino
PhD in Immunology, specialized in Virology
As a scientific writer, Ana is passionate about bridging the gap
between research and real-world impact. With expertise in immunology, virology,
oncology, and clinical studies, she makes complex science clear and accessible.
Her mission: to accelerate knowledge sharing and empower evidence-based
decisions through impactful communication. 
